rs137853221
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PP3_StrongPP5
The NM_000515.5(GH1):c.413A>G(p.Asp138Gly) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D138E) has been classified as Uncertain significance.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
GH1
NM_000515.5 missense
NM_000515.5 missense
Scores
4
8
5
Clinical Significance
Conservation
PhyloP100: 5.28
Genes affected
GH1 (HGNC:4261): (growth hormone 1) The protein encoded by this gene is a member of the somatotropin/prolactin family of hormones which play an important role in growth control. The gene, along with four other related genes, is located at the growth hormone locus on chromosome 17 where they are interspersed in the same transcriptional orientation; an arrangement which is thought to have evolved by a series of gene duplications. The five genes share a remarkably high degree of sequence identity. Alternative splicing generates additional isoforms of each of the five growth hormones, leading to further diversity and potential for specialization. This particular family member is expressed in the pituitary but not in placental tissue as is the case for the other four genes in the growth hormone locus. Mutations in or deletions of the gene lead to growth hormone deficiency and short stature. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.96
PP5
?
Variant 17-63917803-T-C is Pathogenic according to our data. Variant chr17-63917803-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 15974.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GH1 | NM_000515.5 | c.413A>G | p.Asp138Gly | missense_variant | 4/5 | ENST00000323322.10 | |
LOC112268204 | XR_002958148.2 | n.402T>C | non_coding_transcript_exon_variant | 3/3 | |||
GH1 | NM_022559.4 | c.368A>G | p.Asp123Gly | missense_variant | 4/5 | ||
GH1 | NM_022560.4 | c.293A>G | p.Asp98Gly | missense_variant | 3/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GH1 | ENST00000323322.10 | c.413A>G | p.Asp138Gly | missense_variant | 4/5 | 1 | NM_000515.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1461884Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0AN XY: 727242
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1461884
Hom.:
Cov.:
35
AF XY:
AC XY:
0
AN XY:
727242
Gnomad4 AFR exome
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Gnomad4 FIN exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
Bravo
AF:
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Short stature due to growth hormone qualitative anomaly Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 01, 1997 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
A;A;A;A;A
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
0.042
.;.;B
Vest4
MutPred
0.84
.;.;Gain of catalytic residue at N135 (P = 0.0901);
MVP
MPC
0.15
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at